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Class A PBPs accomplish cell wall synthesis to enable bacterial growth and are subject to inhibition by penicillin-type antibiotics. Here, authors leverage single-molecule and bioengineering approaches to show how these essential enzymes are regulated by cognate lipoprotein cofactors.

McCreery, Stubb et al. show that mechano-osmotic changes in the nucleus induce general transcriptional repression and prime chromatin for cell fate transitions by relieving repression of specific differentiation genes.

Successful approaches for controlling gene expression modulate mRNA synthesis by coupling it to inducible transcription effectors. Here the authors design 27 non-natural and non-synonymous transcription factors.

Evolutionary coupling-enabled molecular replacement determination of the structure of Thermus thermophilus RodA reveals a highly conserved cavity in its transmembrane domain, and mutagenesis experiments in Bacillus subtilis and Escherichia coli show that perturbation of this cavity abolishes RodA function.

The ability to design functional sequences is central to protein engineering and biotherapeutics. Here the authors introduce a deep generative alignment-free model for sequence design applied to highly variable regions and design and test a diverse nanobody library with improved properties for selection experiments.

Memory is a basic tenet of intelligent biological systems. Here the authors engineered a programmable and expandable iteration of recombinase-based synthetic memory (interception) that functions post-translation, resulting in faster recombination.

Hailong, an anti-phage defence system, synthesizes an oligodeoxyadenylate signal that blocks effector activity in the absence of phage infection but is degraded by phage-encoded DNA exonucleases, leading to protective growth arrest of infected cells.

The RXFP1 relaxin receptor is a critical mediator of physiological adaptation to pregnancy and an emerging drug target. RXFP1 activation was found to entail an unexpected mechanism of ectodomain disinhibition resulting in downstream signaling.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

The validation and analysis of X-ray crystallographic data is essential for reproducibility and the development of crystallographic methods. Here, the authors describe a repository for crystallographic datasets and demonstrate some of the ways it could serve the crystallographic community.

A high-throughput method leveraging the Illumina HiSeq platform to screen in the order of 10⁸ individual antibody–antigen interactions within 3 days facilitates the rapid discovery of antibodies to clinically relevant targets.

Autonomous hypermutation yeast surface display (AHEAD) mimics the process of somatic hypermutation in animals to enable the rapid in vitro evolution of antibodies, including nanobodies targeting the RBD of SARS-CoV-2.

A newly developed maternally selective nanobody antagonist against the angiotensin II type I receptor stabilizes the receptor in a hybrid conformation and simultaneously binds with specific small-molecule antagonists.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

A mechanism of lipid transport inhibition has been identified for a class of peptide antibiotics effective against resistant Acinetobacter strains, which may have applications in the inhibition of other Gram-negative pathogens.

Coordination of cell wall assembly is critical for bacterial morphology and survival. Here, the authors show that activation of cell wall synthesis by the Rod complex is regulated by the structural dynamics of RodA-PBP2.

Off-target binding hinders the development of therapeutic antibodies and reproducibility in basic research settings. Here the authors develop a method to quantify and reduce the polyreactivity of antibody fragments based on protein sequence alone.

The X-ray crystal structure of the M2 muscarinic acetylcholine receptor, which is essential for the physiological control of cardiovascular function, is reported.

Crystal structures of the σ₂ receptor are determined and used to perform a docking screen of nearly 500 million molecules, identifying σ₂-selective ligands and providing insight into the role of σ₂ in neuropathic pain.

A transiting planet with a period of about 8.5 days and a radius 0.4 times that of Jupiter is reported within the debris disk around the star AU Microscopii.

Very little is known about how a G-protein-coupled receptor (GPCR) transitions from an inactive to an active state, but this study has solved the X-ray crystal structures of the human M2 muscarinic acetylcholine receptor bound to a high-affinity agonist in an active state and to a high-affinity agonist and a small-molecule allosteric modulator in an active state; the structures provide insights into the activation mechanism and allosteric modulation of muscarinic receptors.

The X-ray crystal structure of the mouse δ-opioid receptor in complex with the subtype-selective antagonist naltrindole is reported.

Crystal structures of human σ1 receptor bound to the antagonists haloperidol and NE-100, and to agonist (+)-pentazocine, alongside MD simulations, reveal a unique binding pose for, and major conformational rearrangements induced by, the agonist.

Multi-omic time course experiments reveal intricate biology of salt stress response mechanisms of the historically and industrially relevant algae, Scenedesmus obliquus UTEX393.

Georgia Chenevix-Trench and colleagues report meta-analyses of genome-wide association studies identifying six loci newly associated with epithelial ovarian cancer (EOC). They also test variants at the 12 known and 6 new EOC susceptibility loci for association in BRCA1 and BRCA2 mutation carriers.

Germination of Bacillus subtilis spores in response to L-alanine requires a putative membrane receptor consisting of three proteins. Here, Artzi et al. use evolutionary co-variation analysis and functional assays of mutants to provide evidence that one of the proteins, GerAB, likely acts as the L-alanine sensor.

Chiea Chuen Khor, Tin Aung, Francesca Pasutto, Janey Wiggs and colleagues report a global genome-wide association study of exfoliation syndrome and a fine-mapping analysis of a previously identified disease-associated locus, LOXL1. They identify a rare protective variant in LOXL1 exclusive to the Japanese population and five new common variant susceptibility loci.

The crystal structure of the mouse μ-opioid receptor bound to an antagonist is described, with possible implications for the future development of analgesics.

The X-ray crystal structure of the M3 muscarinic acetylcholine receptor bound to the bronchodilator drug tiotropium is reported; comparison of this structure with that of the M2 muscarinic acetylcholine receptor reveals key differences that could potentially be exploited to develop subtype-selective drugs.

Water thermodynamics drive changes in macromolecular assembly that rapidly restore intracellular water availability in response to physiological fluctuations in temperature, pressure and osmotic strength.

Roger Milne and colleagues conduct a genome-wide association study for estrogen receptor (ER)-negative breast cancer combined with BRCA1 mutation carriers in a large cohort. They identify ten new risk variants and find high genetic correlation between breast cancer risk for BRCA1 mutation carriers and risk of ER-negative breast cancer in the general population.

ADGRF1 is an adhesion GPCR that signals when a bound ligand induces liberation of an intramolecular tethered agonist. Here, the authors show that ADGRF1 can signal though all major G protein classes and identify a structural basis for Gq selectivity.

Crystal structures of a five-protein complex comprising the inner-membrane components of the bacterial lipopolysaccharide transporter provide insight into the mechanism of extraction of lipopolysaccharide from the inner membrane and its transport to the outer membrane.

SEDS proteins are core peptidoglycan polymerases involved in bacterial cell wall elongation and division.

The crystal structure of β-arrestin-1 in complex with a fully phosphorylated 29-amino-acid carboxy-terminal peptide derived from the V2 vasopressin receptor is reported; the structure of the complex shows striking conformational differences in β-arrestin-1 when compared with its inactive conformation.

X-ray crystallography, electron microscopy and functional experiments reveal the details of how KCTD proteins interact with GABA_B receptors and desensitize G-protein-coupled inwardly rectifying potassium channels.

This article describes the growing and invaluable contribution that quantitative mathematical frameworks are making to generating and testing hypotheses in developmental biology, and in shaping new ways of understanding developmental processes across molecular, cellular and tissue scales.

Readily synthesized maltose–neopentyl glycol (MNG) amphiphiles are useful reagents for stabilizing, extracting and crystallizing a variety of integral membrane proteins and have favorable properties relative to conventional detergents.

The crystal structure of the RodA–PBP2 complex from Thermus thermophilus elucidates how binding between these two proteins regulates their abilities to polymerize and crosslink peptidoglycan during bacterial cell wall synthesis.

Here, by developing a high-affinity camelid antibody fragment that stabilizes the active state of the β₂-adrenoceptor, the X-ray crystal structures of the receptor in complex with three agonists, including adrenaline, were determined.

Including participants from 45 countries, Bago et al. find that the situational factors that affect moral reasoning are shared across countries, with diminished observed cultural variation.

The X-ray crystal structures of the human σ1 receptor bound to two different ligands are reported, revealing the overall architecture, oligomerization state, and molecular basis for ligand recognition by this protein.

Yeast surface display platform allows nanobody discovery within two to three weeks. Examples include nanobodies for crystallographic applications, targeting nonpurified antigen or conformationally selective nanobodies to two distinct human GPCRs.